High levels of squalene epoxidase (SQLE) mRNA correlate with a poor tamoxifen therapy response in estrogen positive breast cancer. The current meta-analysis of breast cancer gene-expression and clinical data is the very first study to link the cholesterol biosynthesis pathway to endocrine therapy response in breast cancer.

1. Is cholesterol biosynthesis linked to endocrine therapy response in breast cancer? A study by Helms et al. in 2008 linked the cholesterol biosynthesis pathway to breast cancer 1. Namely, this study found that the mRNA of squaleneepoxidase (SQLE), one of the enzymes in cholesterol biosynthesis pathway, is (1)upregulated in poor prognosis breast cancer, and (2) indicates the high-risk estrogen-positive (ER+) breast cancer, which might benefit from therapies other than endocrine therapy. The above article prompted me to meta-analyze the ER+ breast cancer in regard to SQLE mRNA levels and response to tamoxifen, the standard endocrine therapy in ER+ breast cancer. My meta-analysis demonstrates that the SQLE mRNA significantly associate with (1) distant relapse, and (2) disease free survival in ER+ breast cancer treated with tamoxifen as adjuvant endocrine therapy (Fig. 1). In brief, tumor samples with elevated SQLE mRNA levels originate from patients who respond poorly to tamoxifen endocrine therapy. About 13 million people in the U.S. take statins to lower their cholesterol levels. Past studies show that statins do not significantly modify breast cancer risk. It would be, however, interesting to carry out a prospective study to determine if statins modify breast cancer treatment responses including tamoxifen response. -MehisPold, M.D. mehisp@hotmail.com September 22, 2010 Low SQLE (n = 208) High SQLE (n = 90) Figure 1. Onset of distant relapse is more likely in Tamoxifen-treated ER+ patients with elevated levels of SQLE mRNA (GEO dataset: GSE17705, total number of expression profiles = 298). The top 30% of SQLE mRNA levels in this set were considered High, the rest was considered Low. X-axis: time to distant relapse, Y-axis: 1 – probability of distant relapse. Similar results emerged from an unrelated breast cancer data set. Namely, a GEO set GSE12093 containing 136 ER+ patient profiles annotated for both SQLE and disease free survival produced the following statistics: P = 0.0009 (Log-rank, statistic = 11, D.F. = 1), P = 0.0003 (Wilcoxon, statistic = 13, D.F.=1); High SQLE (n=42), Low SQLE (n=94). Data analysis was carried out in EpiInfo (version 3.5.1). Copyright © Eomix, Inc.